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HUMAN PLURIPOTENT STEM CELL DERIVED NEURODEGENERATIVE DISEASE MODELS ON A MICROFLUIDIC CHIP

机译:人多能干细胞衍生在微流体芯片上的神经变性疾病模型

摘要

Described herein is a microphysiological system for models of disease. Specifically, induced pluripotent stem cells (iPSCs) and iPSC-derived cells, including those obtained from disease patients, are seeded onto microfluidic “chip” devices to study cellular development and disease pathogenesis. Herein, neurodegenerative disease modeling, including Parkinson's Disease (PD) is shown to reproduce key PD pathology in a vascularized human model that contains neurons relating to PD pathology. Such compositions and methods are used for research for PD biomarkers, patient screening for PD risk assessment, and therapeutic discovery and testing. A panel of biomarkers are generated through analysis of living PD-chips by neural activity, whole transcriptomic, proteomic, and metabolomic analysis, and functional enzyme tests of media and tissue. Introducing therapeutics through a vasculature channel, coupled with blood brain barrier penetration studies can be assessed for efficacy in the human neural cells present in the PD-Chip.
机译:本文描述的是疾病模型的微生物生理系统。具体地,诱导的多能干细胞(IPSC)和IPSC衍生的细胞,包括从疾病患者获得的细胞,被接种在微流体“芯片”装置上,以研究细胞发育和病理发生。这里,神经退行性疾病建模包括帕金森病(Pd)在血管化人模型中繁殖关键PD病理学,含有与PD病理学有关的神经元。这些组合物和方法用于研究PD生物标志物,患者筛选PD风险评估以及治疗性发现和测试。通过通过神经活动,整个转录组,蛋白质组学和代谢组分分析,通过神经活性,整个转录组,蛋白质组学和代谢组分析,以及培养基和组织的功能酶试验来产生一组生物标志物。通过脉管系统引入治疗方法,可以评估PD芯片中存在的人神经细胞中的疗效的疗效可以评估血脑屏障渗透性研究。

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